Galantamine reduces striatal degeneration in 3-nitropropionic acid model of Huntington's disease.
The acetylcholinesterase inhibitor (AChEI) galantamine is currently used to treat mild to moderate Alzheimer's disease (AD), and it has been suggested to have several neuroprotective effects. To investigate the potential application of this drug to the treatment of Huntington's disease, we examined whether galantamine can reduce the striatal degeneration induced by the mitochondrial toxin, 3-nitropropionic acid (3NP). 3NP (63 mg/kg/day) was delivered to Lewis rats by osmotic pumps for 5 consecutive days, and the rats received intraperitoneal administration of either different concentrations of galantamine (1mg/kg/day or 10 mg/kg/day, twice daily) or vehicle (saline) throughout the experiment. Galantamine attenuated the 3NP-induced neurologic deficits on days 2-5. Galantamine-treated rats showed smaller striatal lesion volumes measured by Nissl staining and lower numbers of TUNEL(+) apoptotic cells when compared to the vehicle-treated rats. Galantamine failed to reduce the striatal lesion volume when co-administered with mecamylamine, a nicotinic acetylcholine receptor antagonist. Our data indicate that galantamine can attenuate neurodegeneration in a Huntington's disease model by modulating nAChR.
Park
Jung-Eun
JE
Neurodegeneration Research Laboratory, Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Lee
Soon-Tae
ST
Im
Woo-Seok
WS
Chu
Kon
K
Kim
Manho
M
D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005702:Galantamine / Q000627:therapeutic use*; D006816:Huntington Disease / Q000139:chemically induced / Q000150:complications*; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D009460:Neurologic Examination; D009574:Nitro Compounds; D018697:Nootropic Agents / Q000627:therapeutic use*; D011422:Propionates; D051381:Rats; D011917:Rats, Inbred Lew; D018709:Statistics, Nonparametric
D009574:Nitro Compounds; D018697:Nootropic Agents; D011422:Propionates; D005702:Galantamine; C015392:3-nitropropionic acid